Relapsed/Refractory MCL

Eventual relapse is inevitable and universal among patients with MCL, necessitating second- and third-line therapies. Ibrutinib exhibits a high overall response rate (68%) in and is considered a standard of care for previously treated patients.


Continue Reading

Bendamustine, usually in combination with rituximab is “the first choice of chemotherapy-based second-line therapy in patients that did not receive bendamustine previously,” according to Dr Martin and colleagues.

“There are 3 drugs approved by the FDA (bortezomib, ibrutinib, and lenalidomide) and multiple other chemotherapy regimens that have demonstrated activity and safety in this setting,” Dr Martin told Cancer Therapy Advisor.

“As many options as there are, there are infinitely more scenarios defined by human diversity and tumor biology. Our job is to consider all of the options and propose those that make the most sense. I always look at all of the options and almost always I find myself believing that the clinical trial is the standard of care.”

Innovations involving chimeric antigen receptor (CAR)-T cell therapy might improve remission rates and are undergoing research in relapsed/refractory MCL.

Biomarkers

Adding Ki67 to the MIPI improved its prognostic power, though other prognostic and treatment-predictive biomarkers are in development.

“Ki67 significantly improves the prognostic ability of the MIPI, which is great,” Dr Martin said. “My impression is that assays of proliferation generally fall into the ‘prognostic’ category. Right now, I think that TP53 mutational analysis probably does as well.”

Dr Martin also expects the development of biomarkers that predict outcomes for different treatments.

“I think that the new generation of studies with targeted molecules will help us to better understand this relationship,” he noted. “For example, TP53 mutation analysis may be very predictive of poor outcome with chemotherapy but not with certain small molecules.”

“Given the multitude of promising drugs being evaluated in MCL, we should expect to see new potential biomarkers described this year,” Dr Martin said. “But the process of evaluating the functional implications of those biomarkers, validating them in larger studies, and trying to overcome them with alternate therapies is where we need to move faster.”

There are multiple approaches to evaluating MRD in research settings, each with its own advantages and disadvantages.

“I’m sure new options will pop up in the future,” Dr Martin said. “I’m more interested in how this kind of assay could be moved into the clinic in a way that would actually benefit patients, not just predict outcome.”

References

  1. Martin P, Ghione P, Dreyling M. Mantel cell lymphoma—current standards of care and future directions. Cancer Treat Rev. 2017 May 27. doi: 10.1016/j.ctrv.2017.05.008 [Epub ahead of print]
  2. Sandoval-Sus JD, Sotomayor EM, Shah BD. Mantle cell lymphoma: contemporary diagnostic and treatment perspectives in the age of personalized medicine. Hematol Oncol Stem Cell Ther. 2017 Apr 6. doi: 10.1016/j.hemonc.2017.02.003 [Epub ahead of print]
  3. Aschebrook-Kilfoy B, Caces DB, Ollberding NJ, Smith SM, Chiu BC. An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA. Leuk Lymphoma. 2013;54(8):1677-83. doi: 10.3109/10428194.2012.760041
  4. Smedby KE, Hjalgrim H. Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes. Semin Cancer Biol. 2011;21(5):293-8. doi: 10.1016/j.semcancer.2011.09.010
  5. Wang Y, Ma S. Racial differences in mantle cell lymphoma in the United States. BMC Cancer. 2014;14:764. doi: 10.1186/1471-2407-14-764
  6. Hermine O, Hoster E, Walewski J, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388(10044):565-75. doi: 10.1016/S0140-6736(16)00739-X
  7. Rummel MJ, Niederle N, Maschmeyer, G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381:1203-10. doi: 10.1016/S0140-6736(12)61763-2
  8. Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015;372:944-53. doi: 10.1056/NEJMoa1412096